Objective To analyze the efficacy and safety of transarterial chemoembolization (TACE) with chemotherapy regimen containing platinum in the treatment of primary liver cancer. Methods 86 patients with advanced hepatocellular carcinoma treated in our hospital from December 2015 to December 2016 were selected and randomly divided into two groups with 43 cases each group. Lipiodol chemotherapy was performed with Lobaplatin, epirubicin hydrochloride and mitomycin in the study group, control group while Lipiodol chemotherapy was performed with oxaliplatin, epirubicin hydrochloride and mitomycin in the control group. The gelatin sponge was used to block tumor blood vessels and the treatment lasted for 2 courses. According to the curative effect evaluation standard of solid tumor (RECIST), the curative effect was evaluated and the adverse reactions were compared between the two groups. Results The total effective rates of the two groups were not significantly different , but the effective rate of the study group (20.93%) was significantly higher than that of the control group (6.98%), and the difference was statistically significant (P<0.05). The incidence of hematologic toxicity in the study group (30.23%) was slightly higher than that in the control group (20.93%), the incidence of gastrointestinal reactions (44.19%) and liver and kidney damage (13.95%) were lower than that of the control group respectively by 60.47% and 25.58%, but there was no significant difference . The incidence of neurotoxicity in the study group (2.33%) was significantly lower than that in the control group (27.91%), and the difference was statistically significant (P<0.05). Conclusion For patients with advanced hepatocellular carcinoma, there was no significant difference between the efficacy and safety of transarterial chemoembolization with chemotherapy regimen containing platinum and oxaliplatin chemotherapy regimen, and adverse reactions are similar, but the incidence of neurotoxicity is low.